Neuronal lipofuscinosis caused by Kufs disease/CLN4 DNAJC5 mutations but not by a CSPα/DNAJC5 deficiency.

ABSTRACT: Kufs disease/CLN4 is an autosomal dominant neurodegenerative disorder caused by unknown mechanisms through Leu¹¹⁵Arg and Leu¹¹⁶Δ mutations in the DNAJC5 gene that encodes the synaptic vesicle co-chaperone cysteine string protein α (CSPα/DNAJC5). To investigate the disease mechanisms in vivo, we generated three independent mouse lines overexpressing different versions of CSPα/DNAJC5 under the neuron-specific Thy1 promoter: wild-type (WT), Leu¹¹⁵Arg, and Leu¹¹⁶Δ. Mice expressing mutant Leu¹¹⁵Arg CSPα/DNAJC5 are viable but develop motor deficits. As described in patients with Kufs disease, we observed the pathological lipofuscinosis and intracellular structures resembling granular osmiophilic deposits (GRODs) in the mutant but not in the

SUBMITTER: Lopez-Begines S 

PROVIDER: S-EPMC12094229 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature